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Mouse oocytes suppress cAMP-induced expression of LH receptor mRNA by granulosa cells in vitro
J J Eppig1, F L Pendola, K Wigglesworth
1Jackson Laboratory, Bar Harbor, Maine 04609, USA. jje@aretha.jax.org
Abstract:
Mouse oocytes suppress follicle-stimulating hormone (FSH)-induced luteinizing hormone receptor (LHR) messenger ribonucleic acid (mRNA) expression in cultured granulosa cells. The objective of this study was to assess the mechanism by which oocytes suppress FSH-induced LHR expression. The effect of cumulus cell-denuded, germinal-vesicle-stage oocytes, isolated from antral follicles, on FSH-induced cyclic adenosine monophosphate (cAMP) production by cultured granulosa cells was determined by radioimmunoassays. In addition, the effect of oocytes on 8Br-cAMP-induced LHR mRNA steady-state expression by granulosa cells was assessed by RNase protection assays. Oocytes had no detectable effect on FSH-induced cAMP production. However, oocytes dramatically suppressed 8Br-cAMP-induced LHR mRNA steady-state expression by granulosa cells. It was concluded that the mechanism by which oocytes suppress FSH-induced steady-state expression of LHR mRNA is not by inactivating FSH, preventing functional interactions of FSH with its granulosa cell receptors, or by interfering with the signal-transduction mechanisms required for FSH-dependent cAMP production. In addition, since oocytes suppressed the 8Br-cAMP-induced increase in steady-state expression of mRNA for LHR, oocyte-derived factors probably suppress expression by acting downstream of FSH-induced elevation of granulosa cell cAMP.
Insights
Mouse oocytes prevent luteinizing hormone receptor (LHR) mRNA expression by acting downstream of cyclic adenosine monophosphate (cAMP) signaling. This suggests oocyte-derived factors regulate granulosa cell gene expression.
Area of Science:
- Reproductive Biology
- Cellular Signaling
- Molecular Endocrinology
Background:
- Oocytes play a crucial role in regulating ovarian function.
- Follicle-stimulating hormone (FSH) induces luteinizing hormone receptor (LHR) expression in granulosa cells, a key event in follicular development.
- The precise mechanism by which oocytes influence FSH-induced LHR expression remains unclear.
Purpose of the Study:
- To investigate the mechanism by which mouse oocytes suppress FSH-induced LHR mRNA expression in granulosa cells.
- To determine if oocytes interfere with FSH signaling pathways upstream or downstream of cAMP production.
Main Methods:
- Granulosa cells were cultured with or without oocytes.
- FSH-induced cyclic adenosine monophosphate (cAMP) production was measured using radioimmunoassays.
- LHR mRNA steady-state levels were assessed by RNase protection assays following stimulation with 8Br-cAMP (a cAMP analog).
Main Results:
- Oocytes did not affect FSH-induced cAMP production in granulosa cells.
- Oocytes significantly suppressed LHR mRNA expression induced by 8Br-cAMP.
- This indicates oocytes do not interfere with FSH binding or initial signal transduction.
Conclusions:
- Oocyte-derived factors suppress FSH-induced LHR mRNA expression by acting downstream of cAMP elevation in granulosa cells.
- The mechanism involves modulation of gene expression at a post-cAMP level.
- Oocytes actively regulate granulosa cell gene expression, impacting reproductive processes.